8 research outputs found

    Opioids depress cortical centers responsible for the volitional control of respiration

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    Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensory-affective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem

    Objectively measuring pain using facial expression: is the technology finally ready?

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    Currently, clinicians observe pain-related behaviors and use patient self-report measures in order to determine pain severity. This paper reviews the evidence when facial expression is used as a measure of pain. We review the literature reporting the relevance of facial expression as a diagnostic measure, which facial movements are indicative of pain, and whether such movements can be reliably used to measure pain. We conclude that although the technology for objective pain measurement is not yet ready for use in clinical settings, the potential benefits to patients in improved pain management, combined with the advances being made in sensor technology and artificial intelligence, provide opportunities for research and innovation

    The nucleoside transporters and adenosine regulation of nociceptive neurotransmission in the mammalian dorsal horn

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    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Evaluation of the Efficacy of Musical Vibroacupuncture in Pain Relief:A Randomized Controlled Pilot Study

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    OBJECTIVES: To investigate if skin vibration employing consonant frequencies emitted by skin transducers attached to a combination of acupuncture points and according to musical harmony (musical chord) produces more significant pain relief compared to just a single frequency. MATERIALS AND METHODS: Skin vibrostimulation produced by five electromagnet transducers was applied at five acupoints traditionally used to pain relief and anxiety in 13 pain-free healthy volunteers using the cold pressor test (CPT). The study consisted of three randomized sessions conducted on alternate days, with participants receiving either simultaneous frequencies of 32, 48, and 64 Hz that equate those used in a musical chord, hereby defined as musical vibroacupuncture (MVA), a single frequency of 32 Hz, set as vibroacupuncture (VA) and sham procedure (SP). CPT scores for pain thresholds and pain tolerance were assessed using repeated-measures ANOVAs. Pain intensity was evaluated using a numerical rating scale (NRS), while sensory and affective aspects of pain were rated using the short-form McGill Pain Questionnaire (SF-MPQ) and State-Trait Anxiety Inventory (STAI) Y-Form. RESULTS: Pain thresholds did not vary significantly between trials. Pain tolerance scores were markedly higher in MVA compared to baseline (p = 0.0043) or SP (p = 0.006) but not for VA. Pain intensity for MVA also differed significantly from the baseline (p = 0.007) or SP (p = 0.027), but not for VA. No significant differences were found in SF-MPQ and STAI questionnaires. CONCLUSIONS: These results suggest that MVA effectively increased pain tolerance and reduced pain intensity when compared with all groups, although not significant to the VA group

    Control of glutamatergic neurotransmission in the rat spinal dorsal horn by the nucleoside transporter ENT1

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    Adenosine modulates nociceptive processing in the superficial dorsal horn of the spinal cord. In other tissues, membrane transporters influence profoundly the extracellular levels of adenosine. To investigate the putative role of nucleoside transporters in the regulation of excitatory synaptic transmission in the dorsal horn, we employed immunohistochemistry and whole-cell patch-clamp recording of substantia gelatinosa neurons in slices of rat spinal cord in vitro. The rat equilibrative nucleoside transporter (rENT1) was revealed by antibody staining to be abundant in neonatal and mature dorsal horn, especially within laminae I-III. This was confirmed by immunoblots of dorsal horn homogenate. Nitrobenzylthioinosine (NBMPR), a potent non-transportable inhibitor of rENT1, attenuated synaptically evoked EPSCs onto lamina II neurons in a concentration-dependent manner. Application of an adenosine A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine produced a parallel rightward shift in the NBMPR concentration-effect curve. The effects of NBMPR were partially reversed by adenosine deaminase, which facilitates the metabolic degradation of adenosine. The modulation by NBMPR of evoked EPSCs was mimicked by exogenous adenosine or the selective A1 receptor agonist, 2-chloro-N6-cyclopentyl adenosine. NBMPR reduced the frequency but not the amplitude of spontaneous miniature EPSCs and increased the paired-pulse ratio of evoked currents, an effect that is consistent with presynaptic modulation. These data provide the first direct evidence that nucleoside transporters are able to critically modulate glutamatergic synaptic transmission
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